CN117229172A - Diquinine compound and synthetic method and application thereof - Google Patents
Diquinine compound and synthetic method and application thereof Download PDFInfo
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- CN117229172A CN117229172A CN202310941743.8A CN202310941743A CN117229172A CN 117229172 A CN117229172 A CN 117229172A CN 202310941743 A CN202310941743 A CN 202310941743A CN 117229172 A CN117229172 A CN 117229172A
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 31
- 238000010189 synthetic method Methods 0.000 title claims description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 77
- 239000003054 catalyst Substances 0.000 claims abstract description 25
- JKJWYKGYGWOAHT-UHFFFAOYSA-N bis(prop-2-enyl) carbonate Chemical compound C=CCOC(=O)OCC=C JKJWYKGYGWOAHT-UHFFFAOYSA-N 0.000 claims abstract description 23
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 20
- 125000003118 aryl group Chemical group 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 12
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 10
- 150000001336 alkenes Chemical class 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 238000001308 synthesis method Methods 0.000 claims abstract description 6
- 241001507673 Penicillium digitatum Species 0.000 claims abstract description 5
- 230000009471 action Effects 0.000 claims abstract description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
- -1 dioxane compound Chemical class 0.000 claims description 20
- 239000007810 chemical reaction solvent Substances 0.000 claims description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- MCEBXXSZFFMJLM-UHFFFAOYSA-N methyl 3-amino-4-bromo-2-nitrobenzoate Chemical group COC(=O)C1=CC=C(Br)C(N)=C1[N+]([O-])=O MCEBXXSZFFMJLM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 241001530056 Athelia rolfsii Species 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 abstract description 3
- 230000005764 inhibitory process Effects 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 230000003647 oxidation Effects 0.000 abstract description 2
- 238000007254 oxidation reaction Methods 0.000 abstract description 2
- 230000009467 reduction Effects 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 229910052723 transition metal Inorganic materials 0.000 abstract description 2
- 150000003624 transition metals Chemical class 0.000 abstract description 2
- 241000813090 Rhizoctonia solani Species 0.000 abstract 2
- 241000228143 Penicillium Species 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 239000002904 solvent Substances 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 16
- 239000003480 eluent Substances 0.000 description 14
- 239000003208 petroleum Substances 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000209094 Oryza Species 0.000 description 3
- 235000007164 Oryza sativa Nutrition 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- WPBUMSXOUUWUAL-UHFFFAOYSA-N benzyl prop-2-enyl carbonate Chemical compound C=CCOC(=O)OCC1=CC=CC=C1 WPBUMSXOUUWUAL-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229930004069 diterpene Natural products 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- SWQDRYKDDGFPLL-UHFFFAOYSA-N tert-butyl prop-2-enyl carbonate Chemical compound CC(C)(C)OC(=O)OCC=C SWQDRYKDDGFPLL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The application discloses a biquageny compound, a synthesis method and application thereof, wherein aryl dicyano alkene and allyl carbonate are used as reaction raw materials, and react under the action of an organic phosphine catalyst to obtain the biquageny compound. The application has the advantages that: the reaction is efficient and the yield is high; the organic phosphine catalyst is cheap and easy to obtain, stable and has no pungent smell; strong acid or strong alkali and an additional oxidation or reduction agent are not needed to be added in the reaction, so that the conditions are mild; the transition metal is not required to be used as a catalyst in the reaction, so that the method is economical, practical and environment-friendly; the reaction substrate is easy to prepare. The compound represented by the formula (III) has better inhibition activity on penicillium digitatum (Penicillium digitaum) and rhizoctonia solani (Rhizoctonia solani), wherein the effect of the compound 11 is best and respectively reaches 91% and 83%.
Description
Technical Field
The application belongs to the technical field of organic compound process application, and particularly relates to a dioxane compound, a high-efficiency simple synthesis method thereof and application thereof in medicines for resisting penicillium digitatum and/or rice sheath blight.
Background
The biquinine is a distinct series of natural products, such as alkaloids and terpenoids, which are building blocks that are widely present in carbocyclic frames. These molecules containing the biquinine class not only exhibit a specific penta-carbocyclic structure, but also exhibit a broad range of biological activities, drawing a broad interest from the world-wide field of organic synthesis. In addition, various natural compounds containing the benzobiquazanes have been found to have significant biological and pharmacological activities. Another natural product, canataxaprop, also containing five and five carbocycles, is a taxane diterpene of important pharmaceutical importance, the most prominent taxol being one of the most clinically used anticancer drugs today, as follows:
the development of simple synthetic strategies for such classes has been a very interesting topic for the organic synthesis community, however few catalytic methods for synthesizing such classes have been reported, and the synthesis of such classes has been very challenging, and the objective of the present application is to design a simple and practical catalytic method for constructing such classes. To our knowledge, organophosphine catalysis is a very excellent catalyst in cyclization reactions, often referred to as a high efficiency catalyst for cyclization reactions. Therefore, the application splits the mother nucleus structure into raw materials of aryl dicyano alkene and allyl carbonate, and constructs the mother nucleus structure through the catalysis of organic phosphine.
Disclosure of Invention
The application innovatively realizes a method for efficiently constructing the biquinine. The inventor discovers that the aryl dicyano alkene is a very active aryl compound containing electron withdrawing groups, and has the characteristics of stability, easiness in preparation and the like. In view of this, the present application devised a reaction process for preparing a bisquinine compound by reacting an aryldicyanoalkene with an allyl carbonate.
According to the synthesis method of the biquinine compound, in the presence of the catalyst of the organic phosphine, aryl dicyano alkene and allyl carbonate are used as reaction raw materials, and the reaction is carried out in a reaction solvent, so that the corresponding conversion is effectively realized, and the biquinine compound shown in a figure (III) is prepared. Wherein the reaction process is shown in the following reaction formula a:
wherein R is 1 Is any one of 2-nitro, 4-nitro, 5-fluoro-2-nitro, 5-chloro-2-nitro, 5-bromo-2-nitro, 4-fluoro-2-nitro, 4-chloro-2-nitro, 4-bromo-2-nitro and 4-methyl formate. R is R 2 Is any one of ethyl, isopropyl, n-butyl, tert-butyl, benzyl and cyclohexyl.
As shown in the reaction formula a, the application uses aryl dicyano alkene shown in the formula (I) and allyl carbonate as reaction raw materials, and reacts in a reaction solvent under the action of an organic phosphine catalyst to obtain the biquinine compound shown in the formula (III).
In the application, the ratio of the initial raw material shown in the figure (I) to the raw material shown in the figure (II) of the allyl carbonate is 1:2-3.
In the present application, the solvent is any one of dichloromethane, dichloroethane, chloroform, toluene, acetonitrile and acetone. From the standpoint of the reaction effect of the product, acetone is selected as the solvent.
The synthesis reaction of the application comprises the following steps:
the reaction of equation a includes the steps of: adding aryl dicyano alkene, allyl carbonate and acetone into a reaction container, and stirring at normal temperature (about 25 ℃ in general) to react to obtain the biquinine compound shown in the figure (III).
In one embodiment, as in equation a, the synthesis reaction of the present application is carried out by adding aryldicyano alkene (X mmol), allyl carbonate (Y mmol), solvent (V mL) to reaction flask A and stirring the reaction system at 25deg.C for 12 hours. After the reaction is finished, the reaction system is concentrated, and the target product is obtained through column chromatography separation.
The application also provides the biquinine compound which is prepared by the synthesis method and is shown in a figure (III).
Wherein R is 1 Is halogen atom substituted; r is R 2 Is an alkyl or aryl group.
The application also provides an application method of the biquinine compound shown in the (III) in synthesizing the related potential medicine containing the biquinine.
The application has the following advantages: 1. the reaction is efficient, and the yield is high; 2. the organic phosphine catalyst is cheap and easy to obtain, stable and has no pungent smell; 3. strong acid or strong alkali and an additional oxidation or reduction agent are not needed to be added in the reaction, so that the conditions are mild; 4. the transition metal is not required to be used as a catalyst in the reaction, so that the method is economical, practical and environment-friendly; 5. the reaction substrate is easy to prepare; 6. the reaction efficiency is high after the reaction is amplified, and the method has practical value.
According to the application, an aryl dicyanoene compound and an allyl carbonate compound which are easy to prepare are used as reaction raw materials, and react under the action of an organic phosphine catalyst to obtain the biquagenane compound. The reaction operation is simple, the condition is mild, and the method is suitable for large-scale industrial production.
Detailed Description
The present application will be described in further detail with reference to the following specific examples, to which the present application is not limited. Variations and advantages that would occur to one skilled in the art are included in the application without departing from the spirit and scope of the inventive concept, and the scope of the application is defined by the appended claims. The procedures, conditions, reagents, experimental methods, etc. for carrying out the present application are common knowledge and common knowledge in the art, except for those specifically mentioned below, and the present application is not particularly limited. The data presented in the examples below include specific operations and reaction conditions and products. The purity of the product was identified by nuclear magnetism.
The synthesis reaction of the aryl alkyl thioether compound comprises the following steps:
as shown in equation a: adding o-nitrophenyldicyano-ene, allyl carbonate and acetone into a reaction vessel, and stirring and reacting at normal temperature to obtain the biquinine compound shown in (III). Concentrating, and separating by column chromatography to obtain the target product.
The biquinine compounds shown in table 1 are all products synthesized by the method of the application, and no public literature is available for revealing the compounds.
TABLE 1 novel Diquinine compounds of the application
Example 1
After addition of the ortho-nitro substituted dicyanophenyl alkene (19.9 mg,0.1mmol,1.0 equiv.) with the reaction solvent acetone (1.0 mL) to the reaction tube, the Boc-protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from the solvent under reduced pressure and separated by column chromatography to give product 1 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 93%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ8.01(dd,J＝8.4,1.2Hz,1H),7.84(d,J＝7.6Hz,1H),7.77–7.73(m,1H),7.59–7.55(m,1H),6.69(dd,J＝4.0,2.0Hz,1H),4.59(d,J＝6.4Hz,1H),4.36(d,J＝6.4Hz,1H),4.29(t,J＝6.8Hz,2H),4.07–4.01(m,1H),3.90–3.84(m,1H),3.49(d,J＝13.6Hz,1H),3.06(dt,J＝19.6,1.6Hz,1H),2.92(dt,J＝19.6,2.8Hz,1H),2.58(d,J＝13.6Hz,1H),1.75–1.71(m,2H),1.47–1.40(m,2H),1.36–1.32(m,2H),1.20–1.14(m,2H),0.98(t,J＝7.4Hz,3H),0.82(t,J＝7.2Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.6,163.1,149.8,140.3,137.2,133.4,131.2,129.8,129.6,125.2,114.2,113.5,66.6,64.8,59.5,58.8,53.5,47.2,44.4,41.8,30.4,30.2,19.2,18.9,13.7,13.6.HRMS(ESI)m/z:calcd.for C 26 H 29 N 3 O 6 H + (M+H) + 514.1973,found 514.1978.
example 2
After adding m-nitro substituted dicyanophenyl alkene (19.9 mg,0.1mmol,1.0 equiv.) and reaction solvent acetone (1.0 mL) to the reaction tube, boc-protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from the solvent under reduced pressure and separated by column chromatography to give product 2 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 51%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ8.36(t,J＝2.0Hz,1H),8.29(dd,J＝8.4,1.6Hz,1H),7.86(d,J＝8.0Hz,1H),7.66(t,J＝8.0Hz,1H),6.72(dd,J＝4.0,2.0Hz,1H),4.52(dd,J＝7.2,1.6Hz,1H),4.33–4.26(m,2H),4.00–3.94(m,1H),3.91–3.85(m,1H),3.74(d,J＝7.2Hz,1H),3.57(d,J＝13.6,1H),3.01(dt,J＝19.6,2.0Hz,1H),2.86(dt,J＝19.6,2.8Hz,1H),2.46(d,J＝13.6Hz,1H),1.78–1.71(m,2H),1.47–1.41(m,2H),1.34–1.29(m,2H),1.20–1.14(m,2H),0.98(t,J＝7.6Hz,3H),0.82(t,J＝7.2Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.3,163.1,148.4,140.5,137.6,137.1,134.4,130.0,124.0,123.5,114.4,112.8,66.7,64.8,61.0,59.0,57.0,46.6,44.4,42.6,30.4,30.3,19.2,19.0,13.7,13.6.HRMS(ESI)m/z:calcd.for C 26 H 29 N 3 O 6 H + (M+H) + 514.1973,found 514.1978.
example 3
After adding p-nitro-substituted dicyanophenyl alkene (19.9 mg,0.1mmol,1.0 equiv.) and acetone (1.0 mL), a reaction solvent, was added to the reaction tube, boc-protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added, followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from the solvent under reduced pressure and separated by column chromatography to give product 3 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 59 percent,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ8.32(d,J＝8.8Hz,2H),7.68(d,J＝8.8Hz,2H),6.70(dd,J＝4.0,2.0Hz,1H),4.53(dd,J＝7.6,1.6Hz,1H),4.31–4.25(m,2H),4.00–3.85(m,2H),3.71(d,J＝7.6Hz,1H),3.57(d,J＝13.6Hz,1H),2.98(dt,J＝19.6,2.4Hz,1H),2.85(dt,J＝19.6,2.8Hz,1H),2.45(d,J＝13.6Hz,1H),1.76–1.70(m,2H),1.47–1.41(m,2H),1.34–1.28(m,2H),1.22–1.15(m,2H),0.98(t,J＝7.2Hz,3H),0.82(t,J＝7.6Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.3,163.1,148.2,142.5,140.2,137.2,129.5,124.1,114.3,112.8,66.7,64.9,61.1,59.1,56.8,46.7,44.4,42.6,30.4,30.3,19.2,19.0,13.7,13.6.HRMS(ESI)m/z:calcd.for C 26 H 29 N 3 O 6 Na + (M+Na) + 502.1949,found 502.1960.
example 4
5-fluoro-2-nitro substituted dicyanophenyl alkene (21.7 mg,0.1mmol,1.0 equiv.) and solvent acetone (1.0 mL) were added to the reaction tube, boc protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added, followed by phosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. Then the reaction solution is reducedThe solvent was removed under pressure and separated by column chromatography to give product 4 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 61%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ8.12(dd,J＝9.2,5.2Hz,1H),7.58(dd,J＝9.2,2.4Hz,1H),7.26–7.22(m,1H),6.69(d,J＝2.0Hz,1H),4.71(d,J＝6.4Hz,1H),4.30(t,J＝6.8Hz,3H),4.08–4.01(m,1H),3.95–3.89(m,1H),3.47(d,J＝14.0Hz,1H),3.11(d,J＝19.6Hz,1H),2.93(dt,J＝20.0,2.4Hz,1H),2.61(d,J＝14.0Hz,1H),1.78–1.71(m,2H),1.46–1.39(m,4H),1.24–1.19(m,2H),0.98(t,J＝7.2Hz,3H),0.85(t,J＝7.2Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.4,163.1(d,J＝23.4Hz),140.5,136.9,135.1(d,J＝8.7Hz),128.3(d,J＝9.8Hz),117.4(d,J＝24.8Hz),116.8(d,J＝22.8Hz),114.1,113.3,66.8,59.6,58.8,53.4,47.3,44.3,41.7,30.4,30.3,19.2,19.0,13.6,13.6.HRMS(ESI)m/z:calcd.for C 26 H 28 FN 3 O 6 H + (M+H) + 498.2040,found 498.2043.
example 5
After adding 5-chloro-2-nitro-substituted dicyanophenyl alkene (23.3 mg,0.1mmol,1.0 equiv.) and the reaction solvent acetone (1.0 mL) to the reaction tube, boc-protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added, followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from the solvent under reduced pressure and separated by column chromatography to give product 5 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 63%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ8.01(d,J＝8.8Hz,1H),7.83(d,J＝2.0Hz,1H),7.54(dd,J＝8.4,2.0Hz,1H),6.69(dd,J＝4.0,2.0Hz,1H),4.65(d,J＝6.4Hz,1H),4.34–4.27(m,3H),4.28–4.02(m,1H),3.94–3.88(m,1H),3.48(d,J＝14.0Hz,1H),3.11(dt,J＝19.6,1.6Hz,1H),2.93(dt,J＝19.6,2.8Hz,1H),2.59(d,J＝13.6Hz,1H),1.79–1.72(m,2H),1.47–1.39(m,4H),1.23–1.19(m,2H),0.98(t,J＝7.6Hz,3H),0.86(t,J＝7.6Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.4,163.1,147.9,140.1,136.9,133.4,130.1,129.8,126.8,114.1,113.3,66.8,64.9,59.5,58.8,53.3,47.3,44.4,41.7,30.4,30.3,19.2,19.0,13.7,13.6.HRMS(ESI)m/z:calcd.for C 26 H 28 ClN 3 O 6 H + (M+H) + 514.1740,found 514.1748.
example 6
After adding 5-bromo-2-nitro substituted dicyanophenyl alkene (27.8 mg,0.1mmol,1.0 equiv.) and the reaction solvent acetone (1.0 mL) to the reaction tube, boc-protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added, followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from solvent under reduced pressure and separated by column chromatography to give product 6 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 64 percent,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ7.98(d,J＝1.6Hz,1H),7.92(d,J＝8.8Hz,1H),7.70(dd,J＝8.8,2.0Hz,1H),6.69(d,J＝2.0Hz,1H),4.62(d,J＝6.4Hz,1H),4.35–4.28(m,3H),4.08–4.02(m,1H),3.94–3.88(m,1H),3.48(d,J＝14.0Hz,1H),3.11(d,J＝19.6Hz,1H),2.93(dt,J＝19.6,2.4Hz,1H),2.59(d,J＝14.0Hz,1H),1.80–1.72(m,2H),1.42–1.39(m,2H),1.28–1.21(m,4H),0.98(t,J＝7.2Hz,3H),0.86(t,J＝7.2Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.4,163.1,140.6,136.9,133.4,133.1,132.8,128.4,126.7,114.1,113.3,66.8,64.9,59.5,58.8,53.2,47.3,44.4,41.7,30.5,30.4,19.2,19.0,13.7,13.6.HRMS(ESI)m/z:calcd.for C 26 H 28 BrN 3 O 6 H + (M+H) + 558.1235,found 558.1246.
example 7
After adding 4-fluoro-2-nitro substituted dicyanophenyl alkene (21.7 mg,0.1mmol,1.0 equiv.) and reaction solvent acetone (1.0 mL) to a reaction tube, boc protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from solvent under reduced pressure and separated by column chromatography to give product 7 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 63%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ7.89(dd,J＝8.8,5.2Hz,1H),7.75(dd,J＝8.0,2.4Hz,1H),7.49–7.45(m,1H),6.66(d,J＝1.6Hz,1H),4.58(d,J＝6.8Hz,1H),4.28(t,J＝6.8Hz,1H),4.08–4.02(m,1H),3.93–3.87(m,1H),3.49(d,J＝14.0Hz,1H),3.03(d,J＝19.6Hz,1H),2.89(d,J＝19.6Hz,1H),2.56(d,J＝13.6Hz,1H),1.76–1.69(m,2H),1.46–1.37(m,4H),1.24–1.19(m,2H),0.98(t,J＝7.2Hz,3H),0.85(t,J＝7.6Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ173.5,163.2(d,J＝13.3Hz),160.5,150.4,140.1,137.1,131.9(d,J＝8.2Hz),127.3(d,J＝4.1Hz),120.9(d,J＝21.1Hz),114.0(d,J＝53.3Hz),113.1(d,J＝26.4Hz),66.7,64.9,59.5,58.8,53.1,47.2,44.3,41.8,30.4,30.3,19.2,19.0,13.7,13.6.HRMS(ESI)m/z:calcd.for C 26 H 28 FN 3 O 6 H + (M+H) + 498.2040,found 498.2046.
example 8
After adding 4-chloro-2-nitro-substituted dicyanophenyl alkene (23.3 mg,0.1mmol,1.0 equiv.) and the reaction solvent acetone (1.0 mL) to the reaction tube, boc-protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added, followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from solvent under reduced pressure and separated by column chromatography to give product 8 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 64 percent,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ8.00(d,J＝2.4Hz,1H),7.83(d,J＝8.8Hz,1H),7.71(dd,J＝8.4,2.0Hz,1H),6.66(dd,J＝4.0,2.0Hz,1H),4.55(d,J＝6.8Hz,1H),4.28(t,J＝6.8Hz,3H),4.09–4.03(m,1H),3.93–3.87(m,1H),3.50(d,J＝13.6Hz,1H),3.02(dt,J＝19.6,2.0Hz,2H),2.89(dt,J＝19.6,2.4Hz,1H),2.56(d,J＝13.6Hz,1H),1.76–1.69(m,2H),1.46–1.37(m,4H),1.24–1.18(m,2H),0.98(t,J＝7.2Hz,3H),0.85(t,J＝7.2Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.5,163.1,150.1,140.0,137.1,135.6,133.5,131.2,129.6,125.3,113.9,113.4,66.7,64.9,59.3,58.8,53.1,47.3,44.2,41.7,30.4,30.3,19.2,19.0,13.7,13.6.HRMS(ESI)m/z:calcd.for C 26 H 28 ClN 3 O 6 Na + (M+Na) + 536.1560,found 536.1559.
example 9
After adding 4-bromo-2-nitro substituted dicyanophenyl alkene (27.8 mg,0.1mmol,1.0 equiv.) and the reaction solvent acetone (1.0 mL) to the reaction tube, boc-protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added, followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from the solvent under reduced pressure and separated by column chromatography to give the product 9 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 68%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ8.15(d,J＝2.0Hz,1H),7.86(dd,J＝8.8,2.4Hz,1H),7.75(d,J＝8.8Hz,1H),6.66(dd,J＝4.0,2.0Hz,1H),4.53(d,J＝6.8Hz,1H),4.28(t,J＝6.8Hz,3H),4.08–4.02(m,1H),3.93–3.87(m,1H),3.50(d,J＝13.6Hz,1H),3.02(dt,J＝19.6,2.0Hz,1H),2.89(dt,J＝19.6,2.4Hz,1H),2.55(d,J＝13.6Hz,1H),1.74–1.69(m,2H),1.44–1.37(m,4H),1.24–1.18(m,2H),0.98(t,J＝7.6Hz,3H),0.86(t,J＝7.2Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.5,163.1,150.1,140.0,137.1,136.5,131.4,130.1,128.2,123.1,113.9,113.4,66.7,65.0,59.3,58.8,53.2,47.3,44.2,41.6,30.4,30.3,19.2,19.0,13.7,13.6.HRMS(ESI)m/z:calcd.for C 26 H 28 BrN 3 O 6 H + (M+H) + 558.1235,found 558.1246.
example 10
After addition of o-nitropiperonal substituted dicyanophenyl alkene (24.3 mg,0.1mmol,1.0 equiv.) and reaction solvent acetone (1.0 mL) to the reaction tube, boc protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from the solvent under reduced pressure and separated by column chromatography to give the product 10 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 73%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ7.53(s,1H),7.23(s,1H),6.69(dd,J＝4.0,2.4Hz,1H),6.17(s,2H),4.71(d,J＝6.0Hz,1H),4.28(t,J＝6.8Hz,2H),4.08–4.01(m,1H),3.98–3.92(m,1H),3.41(d,J＝14.0Hz,1H),3.12(ddd,J＝19.6,3.6,1.2Hz,1H),2.93(dt,J＝19.6,2.4Hz,1H),2.60(d,J＝13.6Hz,1H),1.75–1.70(m,2H),1.47–1.40(m,4H),1.26–1.23(m,2H),0.97(t,J＝7.2Hz,4H),0.86(t,J＝7.2Hz,4H). 13 C NMR(100MHz,CDCl 3 )δ173.6,163.2,152.0,148.0,144.1,140.5,137.1,127.8,114.4,113.7,108.3,106.2,103.4,66.7,64.9,59.5,58.8,53.8,47.0,44.3,41.8,30.4,30.6,27.4,19.2,19.0,13.7.HRMS(ESI)m/z:calcd.for C 27 H 29 N 3 O 8 Na + (M+Na) + 546.1848,found 546.1847.
example 11
After methyl-p-formate-substituted dicyanophenyl alkene (21.2 mg,0.1mmol,1.0 equiv.) and acetone (1.0 mL), a reaction solvent, were added to a reaction tube, boc-protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added, followed by the addition ofOrganic phosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from the solvent under reduced pressure and separated by column chromatography to give the product 11 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 51%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ8.11(d,J＝8.0Hz,2H),7.55(d,J＝8.0Hz,2H),6.70(d,J＝1.6Hz,1H),4.53(d,J＝6.0Hz,1H),4.30–4.23(m,2H),3.93(s,3H),3.84–3.78(m,1H),3.65(d,J＝7.6Hz,1H),3.55(d,J＝13.6Hz,1H),2.98(dt,J＝19.6,2.0Hz,1H),2.83(dt,J＝19.6,2.8Hz,1H),2.43(d,J＝13.6Hz,1H),1.74–1.69(m,2H),1.47–1.41(m,2H),1.23–1.19(m,2H),1.14–1.09(m,2H),0.97(t,J＝7.6Hz,3H),0.79(t,J＝7.2Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.5,166.5,163.2,140.2,137.5,130.7,130.2,128.4,114.7,113.0,85.2,66.5,64.7,61.4,59.0,56.8,52.2,46.7,44.6,42.7,30.4,30.1,27.4,19.2,18.9,13.7,13.5.HRMS(ESI)m/z:calcd.for C 28 H 32 N 2 O 6 Na + (M+Na) + 515.2153,found 515.2158.
example 12
After adding p-methoxy substituted dicyanophenyl alkene (18.4 mg,0.1mmol,1.0 equiv.) and acetone (1.0 mL), a reaction solvent, to the reaction tube, boc protected allyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from the solvent under reduced pressure and separated by column chromatography to give the product 12 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 43%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ7.38(d,J＝8.8Hz,2H),6.94(d,J＝8.4Hz,2H),6.69(d,J＝2.0Hz,1H),4.45(d,J＝7.6Hz,1H),4.29–4.22(m,2H),3.98–3.92(m,1H),3.87–3.84(m,1H),3.82(s,3H),3.57(d,J＝7.6Hz,1H),3.51(d,J＝13.6Hz,1H),2.98(dt,J＝19.2,1.6Hz,1H),2.81(dt,J＝19.2,2.4Hz,1H),2.40(d,J＝13.6Hz,1H),1.73–1.68(m,2H),1.46–1.40(m,2H),1.29–1.25(m,2H),1.17–1.11(m,2H),0.97(t,J＝7.2Hz,3H),0.81(t,J＝7.2Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ173.8,163.4,160.0,140.1,137.9,129.4,127.3,115.1,114.2,113.4,66.4,64.7,61.1,58.8,57.1,55.2,46.4,44.7,43.1,30.4,30.2,19.2,19.0,13.7,13.6.HRMS(ESI)m/z:calcd.for C 27 H 32 N 2 O 5 H + (M+H) + 465.2389,found 465.2394.
example 13
After addition of the ortho-nitro substituted dicyanophenyl alkene (19.9 mg,0.1mmol,1.0 equiv.) with the reaction solvent acetone (1.0 mL) to the reaction tube, boc-protected allyl tert-butyl carbonate (77.4 mg,0.3mmol,3.0 equiv.) was added followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from the solvent under reduced pressure and separated by column chromatography to give the product 13 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 63%,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ8.00(dd,J＝8.0,1.2Hz,1H),7.88(dd,J＝8.0,0.8Hz,1H),7.77–7.73(m,1H),7.58–7.53(m,1H),6.56(dd,J＝4.4,2.4Hz,1H),4.58(d,J＝6.4Hz,1H),4.31(d,J＝6.0Hz,1H),3.43(d,J＝13.2Hz,1H),2.96(ddd,J＝19.6,4.0,1.6Hz,1H),2.84(dt,J＝19.6,2.8Hz,1H),2.52(d,J＝14.0Hz,1H),1.56(s,9H),1.24(s,9H). 13 C NMR(100MHz,CDCl 3 )δ172.6,162.5,149.8,139.1,139.0,133.4,131.4,129.9,129.5,125.2,114.4,113.6,83.3,81.6,59.7,58.7,53.7,47.4,44.6,41.8,27.9,27.7.HRMS(ESI)m/z:calcd.for C 26 H 29 N 3 O 6 Na + (M+Na) + 502.1949,found 502.1950.
example 14
After addition of the ortho-nitro substituted dicyanophenyl alkene (19.9 mg,0.1mmol,1.0 equiv.) with the reaction solvent acetone (1.0 mL) to the reaction tube, the Boc-protected allylbenzyl carbonate (87.6 mg,0.3mmol,3.0 equiv.) was added followed by the organophosphine catalyst PPh 3 (7.9 mg,30 mol%) was stirred at a reaction temperature of 25℃for 12 hours. The reaction solution was then freed from solvent under reduced pressure and separated by column chromatography to give the product 14 (eluent polarity: petroleum ether/dichloromethane/ethyl acetate=60:40:1). Yield: 81 percent,>20:1d.r.； 1 H NMR(400MHz,CDCl 3 )δ7.90(d,J＝8.0Hz,1H),7.67(d,J＝7.6Hz,1H),7.54(t,J＝7.2Hz,1H),7.46(d,J＝7.6Hz,1H),7.41(s,5H),7.28(d,J＝2.0Hz,2H),7.11(dd,J＝5.2,1.6Hz,2H),6.73(d,J＝1.6Hz,1H),5.29(dd,J＝32.4,12.0Hz,2H),5.08(d,J＝12.4Hz,1H),4.87(d,J＝12.4Hz,1H),4.63(d,J＝6.4Hz,1H),4.35(d,J＝5.6Hz,1H),3.48(d,J＝13.6Hz,1H),3.06(d,J＝19.2Hz,1H),2.91(dt,J＝19.6,2.4Hz,1H),2.57(d,J＝13.6Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ173.2,162.8,149.6,141.0,136.9,135.1,134.7,133.3,131.0,129.7,129.5,128.9,128.9,128.8,128.5,128.3,128.2,125.2,114.2,113.5,68.5,66.7,59.5,58.8,53.5,47.1,44.3,41.8.HRMS(ESI)m/z:calcd.for C 32 H 25 N 3 O 6 Na + (M+Na) + 570.1636,found570.1629.
example 15
Test of bactericidal Activity
The concentration of the compound was 100ppm, a strain agar slice was taken with a punch (5 mm), the mycelium was inoculated face down onto PDA medium containing the compound to be tested, placed in the exact center of the round medium, and three samples were inoculated per sample to be tested. The blank group is a medium without test compound but with the same concentration of DMSO. After being placed in a biochemical incubator and cultured at 25℃for 3 to 5 days, the diameter of colonies on the medium was measured. And (3) observing the influence of the sample to be tested on the growth of hyphae by comparing the sample to be tested with the blank control group, and calculating the inhibition rate of the sample to be tested on the colony growth at 100 mg/L. Inhibition ratio (%) = [ (blank control colony diameter-sample colony diameter to be measured)/(blank colony diameter-punch diameter) ]×100%. The following table shows the results of the assay for some of the compounds:
from the above table, it was found that the effect of compound 11 was best, and the bacteriostatic effects of 91% and 83% were achieved on penicillium digitatum and rice sheath blight, respectively. Other compounds also have remarkable antibacterial effects. In the above-described examples of the present application, compounds 2, 3 have structural similarity with compound 1; compounds 5, 6, 7, 8, 9, 10 have structural similarity to compound 4; compound 12 has structural similarity to compound 11; compound 13 has structural similarity to compound 14, and therefore, it is also predicted by those skilled in the art that the similar compounds have remarkable antibacterial effects on penicillium digitatum and rice sheath blight.
Claims (7)
1. A synthesis method of a biquinine compound is characterized in that aryl dicyano alkene and allyl carbonate are used as reaction raw materials, and react in a reaction solvent under the action of an organic phosphine catalyst to obtain the biquinine compound shown in a formula (III); the reaction process is shown in a reaction formula a:
wherein R is 1 Is halogen atom substituted; r is R 2 Is alkyl or aryl substituted.
2. The synthetic method according to claim 1, wherein the reaction solvent is selected from any one of dichloromethane, dichloroethane, chloroform, toluene, acetonitrile, and acetone.
3. The synthetic method of claim 1 wherein in the reaction, aryl dicyanoalkene R 1 Selected from 2-nitro, 4-nitro, 5-fluoro-2-nitro, 5-chloro-2-nitro, 5-bromo-2-nitroMethyl, 4-fluoro-2-nitro, 4-chloro-2-nitro, 4-bromo-2-nitro, 4-formate; r is R 2 Is selected from ethyl, isopropyl, n-butyl, tert-butyl, benzyl, and cyclohexyl.
4. The method of claim 1, wherein the molar ratio of aryl dicyano alkene to allyl carbonate starting material in the reaction is 1:2-3.
5. A diquagenane compound prepared by the synthesis method of claim 1, which has the structure shown in (iii):
wherein R is 1 Is halogen atom substituted; r is R 2 Is alkyl or aryl substituted.
6. The dioxane compound according to claim 5, wherein the structure is as shown in (III):
wherein R is 1 Any one selected from 2-nitro, 4-nitro, 5-fluoro-2-nitro, 5-chloro-2-nitro, 5-bromo-2-nitro, 4-fluoro-2-nitro, 4-chloro-2-nitro, 4-bromo-2-nitro and 4-methyl formate; r is R 2 Selected from any one of ethyl, isopropyl, n-butyl, tert-butyl, benzyl and cyclohexyl.
7. The use of a biquinine compound according to claim 5 or 6 for the preparation of a medicament against penicillium digitatum and/or banded sclerotial blight.
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